INSULIN RESISTANCE IS INDEPENDENTLY ASSOCIATED WITH SIGNIFICANT HEPATIC FIBROSIS IN ASIAN CHRONIC HEPATITIS C GENOTYPE 2 OR 3 PATIENTS

March 18, 2011

INSULIN RESISTANCE IS INDEPENDENTLY ASSOCIATED WITH SIGNIFICANT HEPATIC FIBROSIS

IN ASIAN CHRONIC HEPATITIS C GENOTYPE 2 OR 3 PATIENTS

K. Patel1,*, AJ. 1, WL. Chuang2, CM. Lee3, CY. Peng4, G.

Shanmuganathan5, S. Thongsawat6, T. Tanwandee7, V. Mahachai8, C. Pramoolsinsap9,

M. Cho10, KH. Han11, SR. Shah12, GR. 13, PJ. 1, E. Pulkstenis14, M.

Subramanian14, JG. McHutchison1

DOI: 10.1111/j.1440-1746.2011.06722.x

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

ABSTRACT

Background: The role of insulin resistance (IR) and hepatic steatosis in

fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data

and few studies have been performed in Asian-region populations. We

retrospectively investigated the relationship between host metabolic variables,

including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC

genotype 2/3 patients.

Methods: 303 treatment-naïve Asian-region patients with CHC Genotype 2/3 were

enrolled in a multicenter phase 3, study of albinterferon alfa-2b plus ribavirin

for 24 weeks. IR was defined as HOMA-IR > 2. Baseline liver biopsy was evaluated

by a single expert histopathologist. Post hoc subgroup logistic regression

modeling selected for independent variables associated with significant fibrosis

(METAVIR stage F2-F4)

Results: IR was available in 263 non-diabetic Asian-region patients (HCV-2 =

171, HCV-3 = 92), and 433 non-Asian region patients (407 “Caucasian”); METAVIR

fibrosis prevalence F0-F1 (minimal fibrosis) = 201(77%) and F2-F4 (significant

fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 =

64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (Interquartile range: 1.2

– 2.7); 100 (38%) of patients had HOMA-IR > 2. Factors independently associated

with significant fibrosis included HOMA-IR (OR = 8.42), necro-inflammatory grade

(OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008).

This was similar to non-Asian region patients, but steatosis was not associated

with significant fibrosis in either cohort.

Conclusions:In this subgroup study of Asian-region HCV Genotype-2 or -3

patients, insulin resistance, along with age, cholesterol levels and

necro-inflammation, but not steatosis may be associated with significant hepatic

fibrosis.

March 18, 2011